Mitochondrial Donation: Does It Work? What Next?

The latest event from PET (the Progress Educational Trust) brought together scientists, ethicists and patient advocates to discuss recent developments in mitochondrial donation, highlighting scientific advances and ethical considerations alongside patient perspectives.

The discussion was chaired by PET director Sarah Norcross, who led the PET campaign for UK law to be changed to permit mitochondrial donation (see BioNews 789, 792 and 826). She opened the event by highlighting a major milestone – eight healthy babies with donated mitochondria have been born in the UK, all of whom have made normal developmental progress and none of whom show any signs of mitochondrial disease (see BioNews 1298).

Norcross also extended a special welcome to Australians in the audience, as Australia is the only country to date besides the UK to legislate specifically for the use of mitochondrial donation in treatment. As in the UK, Australian law permits the use of mitochondrial donation solely for the purpose of avoiding the transmission of mitochondrial disease from mother to child (see BioNews 956, 1124, 1139 and 1143).

The first speaker was Professor Mary Herbert from Monash University, Melbourne. She is a professor of reproductive biology at Monash's Biomedicine Discovery Institute and a pioneer of mitochondrial donation, previously based at Newcastle University.

Professor Herbert discussed the scientific basis, clinical application and outcomes of mitochondrial donation techniques, demonstrating how they can address the challenges of mitochondrial inheritance and reproductive decision-making. She began by explaining how mitochondrial DNA (mtDNA) affects reproduction, highlighting that a key challenge is the unpredictability of mitochondrial disease inheritance. She went on to explain the difference between homoplasmy (when only one type of mtDNA is present) and heteroplasmy (when a mixture of mtDNA variants is present, with a combination of healthy and mutated mtDNA).

Next, Professor Herbert discussed the differences between pronuclear transfer (PNT) – the mitochondrial donation technique that has been used in the UK to date – and preimplantation genetic testing (PGT). She explained that whereas PGT can reduce the risk of mitochondrial disease transmission if women have a relatively low proportion of unhealthy mitochondria, it cannot achieve this if the proportion of unhealthy mitochondria is high – in such instances, PNT can offer a viable reproductive option instead. She also reviewed egg survival rates, embryo transfer outcomes and live birth results for both PNT and PGT.

The second speaker was Professor Sir Doug Turnbull, emeritus professor of neurology at Newcastle University, and another of the pioneers of mitochondrial donation. He began by sharing the story of Sharon Bernadi, who lost seven children to mitochondrial disease.

Professor Turnbull went on to explain the NHS Mitochondrial Reproductive Care Pathway and the steps patients take before being approved for mitochondrial donation. These include assessments at the Mitochondrial Reproductive Advice Clinic (MRAC) and Mitochondrial Assisted Reproductive Technologies (Mito-ART) Clinic, followed by approval from the Human Fertilisation and Embryology Authority. He then described the pregnancy pathway for UK patients using mitochondrial donation, as well as the follow-up process for the children who have been born through this process, which includes an 18-month neurodevelopmental assessment and a five-year review.

Professor Turnbull concluded by outlining potential next steps, emphasising the importance of continuing the programme to closely monitor the development of children with donated mitochondria. Finally, he thanked the support of the patient community and charities like PET and the Lily Foundation for their vital role in campaigning successfully to change UK law on mitochondrial donation.

Following this, we heard from the Lily Foundation's chief executive, Liz Curtis. She explained that her charity is named her her daughter – Lily – who died of mitochondrial disease eight months after being born. The charity is dedicated to helping those affected, funding research and raising awareness, and now supports 1300 families living with mitochondrial disease.

Curtis outlined the charity's activities, including its work to improve diagnosis and find treatments, and its ultimate ambition of finding a cure for mitochondrial disease. She said that one of her proudest moments to date was contributing to the legalisation of mitochondrial donation in the UK, by bringing patient voices and experiences to the campaign. She also described the positive impact of the legal change on affected families.

Finally, Curtis presented the Lily Foundation's ten-year plan, including its vision of establishing a UK Mitochondrial Disease Research Institute – shaped by patients and families – to work towards finding a cure. She explained that through sustained investment and close collaboration between world-class scientists and an engaged patient community, a Mitochondrial Disease Ecosystem could be created.

Norcross then introduced the final speaker Catherine Mills, professor of bioethics at Monash University, who is currently working on the mitoHOPE pilot programme for mitochondrial donation in Australia.

Professor Mills began by acknowledging longstanding debates about mitochondrial donation, but said that her presentation would focus specifically on the ethics of current mitochondrial donation technology. To frame her discussion, she outlined three key areas of tradeoff that are relevant to the legitimacy of mitochondrial donation – the pace of innovation, justice in resource allocation and equity of access.

Considering the pace of innovation, Professor Mills reflected on the tradeoff between safety and speed, asking how best to balance the two. She argued that a key issue is how much uncertainty we are willing to accept, and how to monitor children with donated mitochondria without subjecting them to excessive medical intervention. Overall, she suggested that models for ongoing monitoring should avoid over-medicalisation to be considered ethical.

Next, Professor Mills examined whether mitochondrial donation should be publicly funded, when healthcare resources are limited. She considered the cost/benefit tradeoff, acknowledging that the technology benefits a relatively small number of people at present, but also rebutting this by emphasising that it is impossible to truly measure the immense value the technology brings to families and to the children born.

The final ethical issue raised by Professor Mills was equity of access. She raised concerns about disparities in access to the treatment, noting that the only programme currently available in the UK has strict eligibility criteria. She suggested that, in the future, as the safety and efficacy of the technology are established and further improved, the eligibility criteria could perhaps be broadened. Overall, she concluded that achieving the legitimacy of this technology is an ongoing, collaborative process, and that this process must involve different constituencies including scientists, ethicists and – crucially – patients.

The event ended with a comprehensive Q&A session, during which the panel answered a wide range of questions about the science, medicine, ethics, regulation and future of mitochondrial donation.

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PET is grateful to the Adelphi Genetics Forum, the British Fertility Society, CooperSurgical and the Senior Infertility Nurse Group for supporting this event.